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Pestilence, one of the four Horsemen of the Apocalypse, is a boss which can be encountered instead of a traditional boss in the Caves and Catacombs once the player has beaten the game for the first time (killed Mom). He is a bloated, diseased, and zombie-like being that lazily leans back on his rotting steed as it carries him around.

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Like Sloth, he fires a lobbed projectile similar to IPECAC, which explodes on contact, and does one heart of damage only. As Well, Pestilence says "hey". It also leaves a pool of green creep upon exploding.

After reducing his health to one half, his head is destroyed, leaving his body still mounted on his horse. It still leaves the green puddles of creep wherever it goes and fires the green bombs more rapidly. Also, the horse begins to summon red and black Flies, with the same coughing sound as the Hive (to compensate for the fact that he is no longer able to summon Chargers and Spitties during this phase).

Pestilence quote often erroneously replaces Conquest in popular culture. The actual text of the Revelation describes Conquest as the first of the four horsemen of the Apocalypse (described as a rider with a bow on a white horse (Rev. 6:2)) and makes no mention of Pestilence.

"A Forgotten Horseman" achievement might be a reference to the fact that Conquest is often forgotten in popular culture.

Pestilence is the only horseman in the game that doesn't grab his horse. (Excluding the Headless Horseman)